Article

Coronary Atherosclerosis in Indigenous South American Tsimane: A Cross-Sectional Cohort Study

April 2017
The Lancet 389(10080)

DOI:10.1016/S0140-6736(17)30752-3

Authors:

Hillard Kaplan

Chapman University

Ben Trumble

Arizona State University

Samuel Wann

University of Wisconsin - Milwaukee

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Background: Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. Methods: We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Findings: Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Interpretation: Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. Funding: National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis

Article

Full-text available

May 2023
LIPIDS HEALTH DIS

Background Coronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial. Methods PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies. Results Of the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)]. Conclusions According to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC. Registration number CRD42021292077.

Atherosclerosis in Indigenous Tsimane: A Contemporary Perspective

Chapter

Apr 2023

Cardiovascular diseases (CVDs) are the leading cause of death worldwide today, but are not just a modern phenomenon. To explore the deep roots of CVDs in human history, this book, for the first time, brings together bioarchaeological evidence from different periods, as old as 5000 BC, and geographic locations from Alaska to Northern Africa. Experts in their fields showcase the powerful tool set available to bioarchaeology, which allows a more comprehensive reconstruction of the human past through evidence for disease. The tools include aDNA and histological analyses and digital imaging techniques for studying skeletal and mummified human remains. The insights gained from these studies are not only of value to historical research but also demonstrate how the science of archaeological human remains can provide the long view of the history of disease and contributes to modern biomedical research within the context of evolutionary medicine.

Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations

Article

Mar 2023
P NATL ACAD SCI USA

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Natural Selection of Immune and Metabolic Genes Associated with Health in Two Lowland Bolivian Populations

Article

Full-text available

Dec 2022

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype–phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4 , MUC21 and MUC22 , TOX2 , ANXA6 , and ABCA1 ) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.

Sleep function: an evolutionary perspective

Article

Oct 2022
LANCET NEUROL

Jerome M. Siegel

Prospective epidemiological studies in industrial societies indicate that 7 h of sleep per night in people aged 18 years or older is optimum, with higher and lower amounts of sleep predicting a shorter lifespan. Humans living a hunter-gatherer lifestyle (eg, tribal groups) sleep for 6–8 h per night, with the longest sleep durations in winter. The prevalence of insomnia in hunter-gatherer populations is low (around 2%) compared with the prevalence of insomnia in industrial societies (around 10–30%). Sleep deprivation studies, which are done to gain insights into sleep function, are often confounded by the effects of stress. Consideration of the duration of spontaneous daily sleep across species of mammals, which ranges from 2 h to 20 h, can provide important insights into sleep function without the stress of deprivation. Sleep duration is not related to brain size or cognitive ability. Rather, sleep duration across species is associated with their ecological niche and feeding requirements, indicating a role for wake–sleep balance in food acquisition and energy conservation. Brain temperature drops from waking levels during non-rapid eye movement (non-REM) sleep and rises during REM sleep. Average daily REM sleep time of homeotherm orders is negatively correlated with average body and brain temperature, with the largest amount of REM sleep in egg laying (monotreme) mammals, moderate amounts in pouched (marsupial) mammals, lower amounts in placental mammals, and the lowest amounts in birds. REM sleep might, therefore, have a key role in the regulation of temperature and metabolism of the brain during sleep and in the facilitation of alert awakening.

Debunking the vegan myth: The case for a plant-forward omnivorous whole-foods diet

Article

Aug 2022
PROG CARDIOVASC DIS

Vegan diets are widely promoted as protective against cardiovascular disease (CVD); however, removing all animal foods from a human's diet usually causes unfavorable health consequences. Our hominin ancestors began consuming meat, fish, seafood, and eggs >2 million years ago. Consequently, humans are genetically adapted to procure nutrients from both plant and animal sources. In contrast, veganism is without evolutionary precedent in Homo sapiens species. Strict adherence to a vegan diet causes predictable deficiencies in nutrients including vitamins B12, B2, D, niacin, iron, iodine, zinc, high-quality proteins, omega-3, and calcium. Prolonged strict veganism increases risk for bone fractures, sarcopenia, anemia, and depression. A more logical diet is a plant-forward omnivorous eating pattern that emphasizes generous consumption of natural, unprocessed foods predominantly from plants. To balance this diet, modest amounts of wholesome animal foods, such wild-caught fish/seafood, pasture-raised meat and eggs, and fermented unsweetened dairy should be consumed regularly.

Apolipoprotein-ε4 is associated with higher fecundity in a natural fertility population

Article

Aug 2023

In many populations, the apolipoprotein-ε4 (APOE-ε4) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the APOE-ε4 allele remains prevalent. We assess the impact of APOE-ε4 on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% APOE-ε4 carriers), those with at least one APOE-ε4 allele had 0.3 to 0.5 more children than (ε3/ε3) homozygotes, while those with two APOE-ε4 alleles gave birth to 1.4 to 2.1 more children. APOE-ε4 carriers achieve higher fertility by beginning reproduction 0.8 years earlier and having a 0.23-year shorter interbirth interval. Our findings add to a growing body of literature suggesting a need for studies of populations living in ancestrally relevant environments to assess how alleles that are deleterious in sedentary urban environments may have been maintained by selection throughout human evolutionary history.

Editorial comment equal access for health care for unequal outcome

Article

Jun 2023

Lena Barrera

Energetic costs of testosterone in two subsistence populations

Article

Jun 2023
AM J HUM BIOL

Objective: Testosterone plays a role in mediating energetic trade-offs between growth, maintenance, and reproduction. Investments in a high testosterone phenotype trade-off against other functions, particularly survival-enhancing immune function and cellular repair; thus only individuals in good condition can maintain both a high testosterone phenotype and somatic maintenance. While these effects are observed in experimental manipulations, they are difficult to demonstrate in free-living animals, particularly in humans. We hypothesize that individuals with higher testosterone will have higher energetic expenditures than those with lower testosterone. Methods: Total energetic expenditure (TEE) was quantified using doubly labeled water in n = 40 Tsimane forager-horticulturalists (50% male, 18-87 years) and n = 11 Hadza hunter-gatherers (100% male, 18-65 years), two populations living subsistence lifestyles, high levels of physical activity, and high infectious burden. Urinary testosterone, TEE, body composition, and physical activity were measured to assess potential physical and behavioral costs associated with a high testosterone phenotype. Results: Endogenous male testosterone was significantly associated with energetic expenditure, controlling for fat free mass; a one standard deviation increase in testosterone is associated with the expenditure of an additional 96-240 calories per day. Discussion: These results suggest that a high testosterone phenotype, while beneficial for male reproduction, is also energetically expensive and likely only possible to maintain in healthy males in robust condition.

Food System Transformation and Gut Microbiota Transition: Evidence on Advancing Obesity, Cardiovascular Diseases, and Cancers—A Narrative Review

Article

Full-text available

Jun 2023

Food, a vital component of our daily life, is fundamental to our health and well-being, and the knowledge and practices relating to food have been passed down from countless generations of ancestors. Systems may be used to describe this extremely extensive and varied body of agricultural and gastronomic knowledge that has been gathered via evolutionary processes. The gut microbiota also underwent changes as the food system did, and these alterations had a variety of effects on human health. In recent decades, the gut microbiome has gained attention due to its health benefits as well as its pathological effects on human health. Many studies have shown that a person’s gut microbiota partially determines the nutritional value of food and that diet, in turn, shapes both the microbiota and the microbiome. The current narrative review aims to explain how changes in the food system over time affect the makeup and evolution of the gut microbiota, advancing obesity, cardiovascular disease (CVD), and cancer. After a brief discussion of the food system’s variety and the gut microbiota’s functions, we concentrate on the relationship between the evolution of food system transformation and gut microbiota system transition linked to the increase of non-communicable diseases (NCDs). Finally, we also describe sustainable food system transformation strategies to ensure healthy microbiota composition recovery and maintain the host gut barrier and immune functions to reverse advancing NCDs.

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum

Article

Full-text available

Jun 2023

Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from "primary" versus "secondary" prevention to a "continuum of risk." The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.

Wealth, health and inequality in Agta foragers

Article

Full-text available

May 2023

Background and objectives There is significant evidence from large-scale, industrial and post-industrial societies that greater income and wealth inequality is negatively associated with both population health and increasing health inequalities. However, whether such relationships are inevitable and should be expected to impact the health of small-scale societies as they become more market-integrated is less clear. Methodology Here, using mixed-effect models we explore the relationship between health, wealth, wealth inequality and health inequalities in a small-scale foraging population from the Philippines, the Agta. Results Across 11 camps we find small to moderate degrees of wealth inequality (maximal Gini Coefficient 0.44) which is highest in the most permanent camps, where individuals engage more heavily in the formal market. However, in both adults (n = 161) and children (n = 215) we find little evidence that either wealth or wealth inequality associates with ill health, except for one measure of nutritional condition – red blood cell count. Conclusions and implications We interpret these results in the light of high levels of cooperation among the Agta which may buffer against the detrimental effects of wealth inequality documented in industrial and post-industrial societies. We observe little intergenerational wealth transmission, highlighting the fluid nature of wealth, and thus wealth inequality, particularly in mobile communities. The deterioration of nutritional status, as indicated by red blood cell counts, requires further investigation before concluding the Agta's extensive cooperation networks may be beginning to breakdown in the face of increasing inequality.

On the Inheritance of Microbiome-Deficiency: Paediatric Functional Gastrointestinal Disorders, the Immune System and the Gut-Brain Axis Network of Researchers on the Chemical Emergence of Life (

Article

Full-text available

May 2023

Like the majority of non-communicable diseases that have recently gained attention, functional gastrointestinal (GI) disorders (FGID) in both children and adults are caused by a variety of medical conditions. In general, while it is often thought that common conditions such as obesity may cause other problems, for example, asthma or mental health issues, more consideration needs to be given to the possibility that they could both be brought on by a single underlying problem. Based on the variations in non-communicable disease, in recent years, our group has been revisiting the exact role of the intestinal microbiome within the Vertebrata. While the metabolic products of the microbiome have a role to play in the adult, our tentative conclusion is that the fully functioning, mutualistic microbiome has a primary role: to transfer antigen information from the mother to the neonate in order to calibrate its immune system, allowing it to survive within the microbial environment into which it will emerge. Granted that the microbiome possesses such a function, logic suggests the need for a robust, flexible, mechanism allowing for the partition of nutrition in the mature animal, thus ensuring the continued existence of both the vertebrate host and microbial guest, even under potentially unfavourable conditions. It is feasible that this partition process acts by altering the rate of peristalsis following communication through the gut–brain axis. The final step of this animal–microbiota symbiosis would then be when key microbes are transferred from the female to her progeny, either live offspring or eggs. According to this scheme, each animal inherits twice, once from its parents’ genetic material and once from the mother’s microbiome with the aid of the father’s seminal microbiome, which helps determine the expression of the parental genes. The key point is that the failure of this latter inheritance in humans leads to the distinctive manifestations of functional FGID disorders including inflammation and gut motility disturbances. Furthermore, it seems likely that the critical microbiome–gut association occurs in the first few hours of independent life, in a process that we term handshaking. Note that even if obvious disease in childhood is avoided, the underlying disorders may intrude later in youth or adulthood with immune system disruption coexisting with gut–brain axis issues such as excessive weight gain and poor mental health. In principle, investigating and perhaps supplementing the maternal microbiota provide clinicians with an unprecedented opportunity to intervene in long-term disease processes, even before the child is born.

Labour's pain: strenuous subsistence work, mechanical wear-and-tear and musculoskeletal pain in a non-industrialized population

Article

Full-text available

May 2023

Musculoskeletal pain is the most debilitating human health condition. Neurophysiological pain mechanisms are highly conserved and promote somatic maintenance and learning to avoid future harm. However, some chronic pain might be more common owing to mismatches between modern lifestyles and traits that originally evolved under distinct premodern conditions. To inform assumptions about factors affecting chronic pain vulnerability prior to industrialization, we assess pain prevalence, perceived causes, and predictors among Tsimane forager-horticulturalists. Habitual subsistence work is the primary reported cause of pain throughout life for both sexes, and pain is more common with age, especially in the back, and for those with more musculoskeletal problems. Sex differences in pain are relatively weak, and we find no association between women's reproductive history and pain, contrary to the hypothesis that reproduction causes women's greater pain susceptibility. Age-standardized current pain prevalence is 1.7-8.2 times higher for Tsimane than other select populations, and Tsimane chronic pain prevalence is within the range of variation observed elsewhere. Chronic low back pain is not a 'mismatch disease' limited to post-industrialized populations. Hominin musculoskeletal changes supporting bipedalism probably imposed health costs, which, after millions of years of evolution, remain an epidemiological burden that may be exacerbated by modern conditions.

Arterial hypertension and its covariates among nomadic Raute hunter-gatherers of Western Nepal: a mixed-method study

Article

Full-text available

Mar 2023

Objectives: To determine the prevalence of, and understand the factors associated with, hypertension among the nomadic Raute hunter-gatherers of Western Nepal. Design: A mixed-method study. Setting: The study was carried out at Raute temporary campsites in the Surkhet District of Karnali Province between May and September 2021. Participants: The questionnaire-based survey included all males and non-pregnant females of the nomadic Raute group aged 15 years and above. In-depth interviews were conducted among purposively selected 15 Raute participants and four non-Raute key informants to help explain and enrich the quantitative findings. Outcome measures: The prevalence of hypertension (defined as brachial artery blood pressure of systolic ≥140 mm Hg and/or diastolic ≥90 mm Hg) and its sociodemographic, anthropometric and behavioural covariates. Results: Of the 85 eligible participants, 81 (median age 35 years (IQR: 26-51), 46.9% female) were included in the final analysis. Hypertension was found in 10.5% of females, 48.8% of males and 30.9% of the total population. Current alcohol and tobacco use were high (91.4% and 70.4%, respectively), with concerning high rates among youths. Males, older people, current drinkers and current tobacco users were more likely to have hypertension. Our qualitative analysis suggests that the traditional forest-based Raute economy is gradually transitioning into a cash-based one that heavily relies on government incentives. Consumption of commercial foods, drinks and tobacco products is increasing as their market involvement grows. Conclusion: This study found a high burden of hypertension, alcohol and tobacco use among nomadic Raute hunter-gatherers facing socioeconomic and dietary transitions. Further research is needed to assess the long-term impact of these changes on their health. This study is expected to help appraise concerned policymakers of an emerging health concern and formulate context-specific and culturally sensitive interventions to limit hypertension-related morbidities and mortalities in this endangered population.

Evolutionary mismatch and the role of GxE interactions in human disease

Article

Full-text available

Jan 2023

Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology--the evolutionary mismatch hypothesis--seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.

Evolutionary mismatch and the role of GxE interactions in human disease

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Full-text available

Jan 2023

Oxford Handbook of Evolutionary Medicine

Article

Full-text available

Feb 2019

Medicine is grounded in the natural sciences, among which biology stands out with regard to the understanding of human physiology and conditions that cause dysfunction. Ironically, evolutionary biology is a relatively disregarded field. One reason for this omission is that evolution is deemed a slow process. Indeed, macroanatomical features of our species have changed very little in the last 300,000 years. A more detailed look, however, reveals that novel ecological contingencies, partly in relation to cultural evolution, have brought about subtle changes pertaining to metabolism and immunology, including adaptations to dietary innovations, as well as adaptations to exposure to novel pathogens. Rapid pathogen evolution and evolution of cancer cells cause major problems for the immune system to find adequate responses. Moreover, many adaptations to past ecologies have turned into risk factors for somatic disease and psychological disorder in our modern world (i.e. mismatch), among which epidemics of autoimmune diseases, cardiovascular diseases, diabetes, and obesity, as well as several forms of cancer stand out. In addition, depression, anxiety, and other psychiatric conditions add to the list. The Oxford Handbook of Evolutionary Medicine is a compilation of up-to-date insights into the evolutionary history of ourselves as a species, and how and why our evolved design may convey vulnerability to disease. Written in a classic textbook style, emphasising the physiology and pathophysiology of all major organ systems, the book addresses students as well as scholars in the fields of medicine, biology, anthropology, and psychology.

Orang Asli Health and Lifeways Project (OA HeLP): a cross-sectional cohort study protocol

Article

Full-text available

Sep 2022

Introduction: Non-communicable disease (NCD) risk is influenced by environmental factors that are highly variable worldwide, yet prior research has focused mainly on high-income countries where most people are exposed to relatively homogeneous and static environments. Understanding the scope and complexity of environmental influences on NCD risk around the globe requires more data from people living in diverse and changing environments. Our project will investigate the prevalence and environmental causes of NCDs among the indigenous peoples of Peninsular Malaysia, known collectively as the Orang Asli, who are currently undergoing varying degrees of lifestyle and sociocultural changes that are predicted to increase vulnerability to NCDs, particularly metabolic disorders and musculoskeletal degenerative diseases. Methods and analysis: Biospecimen sampling and screening for a suite of NCDs (eg, cardiovascular disease, type II diabetes, osteoarthritis and osteoporosis), combined with detailed ethnographic work to assess key lifestyle and sociocultural variables (eg, diet, physical activity and wealth), will take place in Orang Asli communities spanning a gradient from remote, traditional villages to acculturated, market-integrated urban areas. Analyses will first test for relationships between environmental variables, NCD risk factors and NCD occurrence to investigate how environmental changes are affecting NCD susceptibility among the Orang Asli. Second, we will examine potential molecular and physiological mechanisms (eg, epigenetics and systemic inflammation) that mediate environmental effects on health. Third, we will identify intrinsic (eg, age and sex) and extrinsic (eg, early-life experiences) factors that predispose certain people to NCDs in the face of environmental change to better understand which Orang Asli are at greatest risk of NCDs. Ethics and dissemination: Approval was obtained from multiple ethical review boards including the Malaysian Ministry of Health. This study follows established principles for ethical biomedical research among vulnerable indigenous communities, including fostering collaboration, building cultural competency, enhancing transparency, supporting capacity building and disseminating research findings.

Evolutionary Approaches in Aging Research

Article

Aug 2022

Melissa Emery Thompson

While evolutionary explanations for aging have been widely acknowledged, the application of evolutionary principles to the practice of aging research has, until recently, been limited. Aging research has been dominated by studies of populations in evolutionarily novel industrialized environments and by use of short-lived animal models that are distantly related to humans. In this review, I address several emerging areas of "evolutionarily relevant" aging research, which provide a valuable complement to conventional biomedical research on aging. Nonhuman primates offer particular value as both translational and comparative models due to their long life spans, shared evolutionary history with humans, and social complexity. Additionally, because the human organism evolved in a radically different environment than that in which most humans live today, studying populations living in diverse ecologies has redefined our understanding of healthy aging by revealing the contribution of industrialized human environments to age-related pathologies.

Strenuous Endurance Exercise and the Heart: Physiological versus Pathological Adaptations

Chapter

Aug 2022

Although the benefits of regular physical activity on cardiovascular health are well established, the effects of strenuous endurance exercise (SEE) have been a matter of debate since ancient times. In this article, we aim to provide a balanced overview of what is known about SEE and the heart—from epidemiological evidence to recent cardiac imaging findings. Lifelong SEE is overall cardioprotective, with endurance master athletes showing in fact a youthful heart. Yet, some lines of research remain open, such as the need to elucidate the time‐course and potential relevance of transient declines in heart function (or increases in biomarkers of cardiac injury) with SEE. The underlying mechanisms and clinical relevance of SEE‐associated atrial fibrillation, myocardial fibrosis, or high coronary artery calcium scores also remain to be elucidated. © 2022 American Physiological Society. Compr Physiol 12:1‐19, 2022. Although the benefits of regular physical activity on cardiovascular health are well established, controversy exists on the potentially detrimental effects of regular strenuous endurance exercise. Strenuous endurance exercise is overall cardioprotective. Indeed, young endurance athletes and even endurance master athletes (individuals >40‐years‐old who have performed high levels of endurance exercise for ≥1–2 decades and still participate in sports competitions) show a healthier cardiovascular system than their nonathlete peers. A transient decline in heart function (along with increases in biomarkers of cardiac injury) is often observed after acute strenuous endurance exercise, although the time course and potential relevance of these findings remain unclear. Regular strenuous endurance exercise has also been associated with an increased incidence of atrial fibrillation, myocardial fibrosis, or high coronary artery calcium scores, although the underlying mechanisms and clinical relevance of these findings also remain to be elucidated.

There Is Urgent Need to Treat Atherosclerotic Cardiovascular Disease Risk Earlier, More Intensively, and with Greater Precision. A Review of Current Practice and Recommendations for Improved Effectiveness.

Article

Full-text available

Aug 2022

Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and is etiologic for such acute cardiovascular events as myocardial infarction, ischemic stroke, unstable angina, and death. ASCVD also impacts risk for dementia, chronic kidney disease peripheral arterial disease and mobility, impaired sexual response, and a host of other visceral impairments that adversely impact the quality and rate of progression of aging. The relationship between low-density lipoprotein cholesterol (LDL-C) and risk for ASCVD is one of the most highly established and investigated issues in the entirety of modern medicine. Elevated LDL-C is a necessary condition for atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, and randomized clinical trials have all validated this association. Yet despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial prevention more seriously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs. Herein we discuss the need to greatly intensify efforts to reduce risk, decrease disease burden, and provide more comprehensive and earlier risk assessment to optimally prevent ASCVD and its complications. Evidence is presented to support that treatment should aim for far lower goals in cholesterol management, should take into account many more factors than commonly employed today and should begin significantly earlier in life.

An area of greatest vulnerability - Recent advances in kidney injury

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Full-text available

Aug 2022

Aila Akosua Kattner

In this issue of the Biomedical Journal the reader is provided with an insight into the latest observations and advances in acute kidney injury as well as chronic kidney disease. The current SARS-CoV-2 variants are reviewed, and the role of long non-coding RNA in HIV therapy is explored. Furthermore, the potential of metabolomics as means to diagnose multiple sclerosis as well as tuberculosis is presented. Other topics of this issue include the restoration of the spermatogonial stem cell niche; atherosclerosis and the use of improved ultrasound images; and the effect of transcranial magnetic stimulation in patients with autism spectrum disorder. Finally, it is shown how continuous passive motion can be used as supportive therapeutic approach in children with cerebral palsy, and minimally invasive surgery is presented as valid alternative in cases of spine metastasis.

Arterial hypertension and its covariates among the Raute nomadic hunter-gatherers of Western Nepal: a population-based mixed-method study

Preprint

Full-text available

Aug 2022

Objectives This study aimed to determine the prevalence of, and understand the factors associated with, hypertension among the Raute nomadic hunter-gatherers of Western Nepal. Design A mixed-method study with quantitative and qualitative analyses. Setting Household survey at Raute temporary camps in the Surkhet District of Karnali Province, Nepal between the period of May to September 2021. Primary and secondary outcome measures The presence of hypertension and its socio-demographic, anthropometric, and behavioral covariates among the participants. Participants For quantitative analysis, all men and non-pregnant women of the nomadic Raute community aged 15 years above were evaluated for hypertension and its covariates. For the qualitative analysis, we purposively selected both Raute and Non-Raute key informants for in-depth interviews to understand, explain and enrich the quantitative findings. Results Of the 85 total eligible participants, 81 [median age 35 years (Interquartile range: 26–51), 46.9% female] were included in the final analysis. The prevalence of hypertension among men, women, and overall was 48.8% (95% confidence interval (CI): 34.4-63.4), 10.5% (95% CI: 3.7–23.1), and 30.9% (95% CI: 21.6–41.5) respectively. Male sex [adjusted Odds Ratio (aOR)=8.05 (95%CI: 2.15–30.11), p=0.002] and increasing age [aOR=1.05 (95% CI: 1.01–1.09), p=0.025] were found significantly associated with hypertension. A large proportion of the participants were current drinkers (91.4%) and tobacco users (70.4%), yet neither of these factors had a significant association with hypertension. Effect of socio-economic transition; changing patterns of alcohol and tobacco use, changing diet and food security; and traditional health care practices were the themes identified in the qualitative analysis. Conclusion This study found a high prevalence of hypertension, alcohol, and tobacco use among Raute nomadic hunter-gatherers facing socio-economic and nutritional transition. Further longitudinal studies and effective culture-centered community-based interventions are urgently needed to reduce the morbidity and mortality associated with hypertension in this endangered indigenous population. Strengths and limitations of this study This is the first study to assess the prevalence of hypertension and to identify factors associated with it in the nomadic Raute population. We used a mixed-method design, where the quantitative study established the prevalence of hypertension and its associated factors, and the qualitative study deepened the understanding of the quantitative findings. Certain important factors such as salt intake, physical activity level, and a few other cardiometabolic risk factors were not assessed partly due to refusal of invasive procedures among the Rautes, and partly due to resource constraints. Interviews taken in language non-native (Nepali) to the Raute may be subject to language bias. Keywords: Hunter-gatherers, Foragers, Hypertension, Blood pressure, Socio-economic transition, Raute

Variability and the form-function framework in evolutionary biomechanics and human locomotion

Article

Full-text available

Jul 2022

Alison A Murray

The form-function conceptual framework, which assumes a strong relationship between the structure of a particular trait and its function, has been crucial for understanding morphological variation and locomotion among extant and fossil species across many disciplines. In biological anthropology, it is the lens through which many important questions and hypotheses have been tackled with respect to relationships between morphology and locomotor kinematics, energetics, and performance. However, it is becoming increasingly evident that the morphologies of fossil hominins, apes, and humans can confer considerable locomotor diversity and flexibility, and can do so with a range of kinematics depending on soft tissue plasticity and environmental and cultural factors. This complexity is not built in to traditional biomechanical or mathematical models of relationships between structure and kinematics or energetics, limiting our interpretation of what bone structure is telling us about behaviour in the past. The nine papers presented in this Special Collection together address some of the challenges that variation in the relationship between form and function pose in evolutionary biomechanics, to better characterize the complexity linking structure and function and to provide tools through which we may begin to incorporate some of this complexity into our functional interpretations.

Impact of Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors on Arterial Stiffness and Vascular Aging—What Do We Know So Far? (A Narrative Review)

Article

Full-text available

May 2022

Vascular aging, early vascular aging or supernormal vascular aging are concepts used for estimating the cardiovascular risk at a certain age. From the famous line of Thomas Sydenham that “a man is as old as his arteries” to the present day, clinical studies in the field of molecular biology of the vasculature have demonstrated the active role of vascular endothelium in the onset of cardiovascular diseases. Arterial stiffness is an important cardiovascular risk factor associated with the occurrence of cardiovascular events and a high risk of morbidity and mortality, especially in the presence of diabetes. Sodium–glucose cotransporter 2 inhibitors decrease arterial stiffness and vascular resistance by decreasing endothelial cell activation, stimulating direct vasorelaxation and ameliorating endothelial dysfunction or expression of pro-atherogenic cells and molecules.

Editorial: The Impact of Dietary Changes on Non-communicable Diseases in Latin America

Article

Full-text available

Apr 2022

Pramil Singh

Applying an evolutionary mismatch framework to understand disease susceptibility

Article

Full-text available

Sep 2023
PLOS BIOL

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools with partnerships with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Sex differences in lipids: A life course approach

Article

Sep 2023
Atherosclerosis

Ordinaries 12: Return to the Pleistocene

Article

Jul 2023

Humans in the Pleistocene faced external threats to survival and reproduction. Beginning with the invention of agriculture early in the Holocene, the human struggle has shifted inward into a battle for self-control. A technology-driven mismatch between human genes and the modern environment is the source of the increased need for self-control. Perhaps paradoxically, technology provides a path to return to the Pleistocene, at least with regard to certain important aspects of human life.

Hunter-gatherer diets and activity as a model for health promotion: Challenges, responses, and confirmations

Article

Jul 2023
EVOL ANTHROPOL

Beginning in 1985, we and others presented estimates of hunter-gatherer (and ultimately ancestral) diet and physical activity, hoping to provide a model for health promotion. The Hunter-Gatherer Model was designed to offset the apparent mismatch between our genes and the current Western-type lifestyle, a mismatch that arguably affects prevalence of many chronic degenerative diseases. The effort has always been controversial and subject to both scientific and popular critiques. The present article (1) addresses eight such challenges, presenting for each how the model has been modified in response, or how the criticism can be rebutted; (2) reviews new epidemiological and experimental evidence (including especially randomized controlled clinical trials); and (3) shows how official recommendations put forth by governments and health authorities have converged toward the model. Such convergence suggests that evolutionary anthropology can make significant contributions to human health.

Eliminating Atherosclerotic Cardiovascular Disease Residual Risk

Article

Full-text available

Jun 2023
EUR HEART J

This is an Invited CardioPulse article.

Comparing Measured Dietary Variation Within and Between Tropical Hunter-Gatherers Groups to the Paleo Diet

Article

Jun 2023
AM J CLIN NUTR

Background: Although human diets varied considerably before agriculture's spread, public perceptions of pre-agricultural diets have been strongly influenced by the Paleo Diet, which prescribes percentage calorie ranges of 19-35% protein, 22-40% carbohydrate, and 28-47% fat, and prohibits foods with added sugar, dairy, grains, most starchy tubers, and legumes. However, the empirical basis for paleolithic nutrition remains unclear, with some of its assumptions challenged by the archaeological record and theoretical first principles. Objective: We assessed the variation in diets among tropical hunter-gatherers, including the effect of collection methods on implied macronutrient percentages. Methods: We analyzed data on animal food, plant food, and honey consumption by weight and kcal from 15 high quality published ethnographic studies representing 11 recent tropical hunter-gatherer groups. We used Bayesian analyses to perform inference and included data collection methods and environmental variables as predictors in our models. Results: Our analyses reveal high levels of variation in animal versus plant foods consumed and in corresponding percentages of protein, fat, and carbohydrates. In addition, studies that weighed food items consumed in and out of camp and across seasons and years reported higher consumption of animal foods, which varied with annual mean temperature. Conclusions: The ethnographic evidence from tropical foragers refutes the concept of circumscribed macronutrient ranges modeling preagricultural diets.

J-shaped Association Between LDL Cholesterol and Cardiovascular Events: A Longitudinal Primary Prevention Cohort of over 2.4 Million People Nationwide

Article

May 2023

Introduction: Low-density lipoprotein (LDL) cholesterol-lowering treatment is beneficial for the secondary or primary prevention of high-risk atherosclerotic cardiovascular disease (ASCVD). However, the prognostic implications of low LDL cholesterol levels in patients without previous ASCVD and without statin use remain elusive. Methods: From a nationwide cohort, 2,432,471 participants without previous ASCVD or statin use were included. For myocardial infarction (MI) and ischemic stroke (IS), participants were followed-up from 2009 to 2018. They were stratified according to 10-year ASCVD risk (<5%, 5%-<7.5%, 7.5%-<20%, and ≥20%) and LDL cholesterol level (<70, 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL). Results: The relationship between LDL cholesterol levels and ASCVD events exhibited a J-shaped curve for both MI and IS. After classification according to the ASCVD risk, this J-shaped relationship was consistently observed for the composite of MI and IS. Participants with an LDL cholesterol level <70 mg/dL showed a higher MI risk than those with a level of 70-99 mg/dL or 100-129 mg/dL in the low-ASCVD risk group. The J-shaped curve between LDL cholesterol levels and MI risk was attenuated across ASCVD risk groups. For IS, participants with an LDL cholesterol level <70 mg/dL demonstrated increased risks compared with those with a level of 70-99 mg/dL, 100-129 mg/dL, or 130-159 mg/dL in the borderline, intermediate, and high ASCVD risk groups, respectively. In contrast, a linear association was observed in participants taking statins. Interestingly, a J-shaped association was observed between LDL cholesterol and high-sensitivity C-reactive protein (hs-CRP) levels; the mean hs-CRP level and the proportion of individuals with increased hs-CRP levels were relatively high among individuals with an LDL cholesterol level <70 mg/dL. Conclusions: Although high LDL cholesterol levels increase the risk of ASCVD, low LDL cholesterol levels do not warrant safety from ASCVD. Therefore, individuals with low LDL cholesterol levels should be carefully monitored.

Atherosclerosis among the Elites: A Bioarchaeological Investigation of Seventeenth- to Nineteenth-Century Mummified Human Remains from Palermo, Sicily (Italy) and Vilnius (Lithuania)

Chapter

Apr 2023

Obesity and the risk of cardiometabolic diseases

Article

Full-text available

Mar 2023

The prevalence of obesity has reached pandemic proportions, and now approximately 25% of adults in Westernized countries have obesity. Recognized as a major health concern, obesity is associated with multiple comorbidities, particularly cardiometabolic disorders. In this Review, we present obesity as an evolutionarily novel condition, summarize the epidemiological evidence on its detrimental cardiometabolic consequences and discuss the major mechanisms involved in the association between obesity and the risk of cardiometabolic diseases. We also examine the role of potential moderators of this association, with evidence for and against the so-called 'metabolically healthy obesity phenotype', the 'fatness but fitness' paradox or the 'obesity paradox'. Although maintenance of optimal cardiometabolic status should be a primary goal in individuals with obesity, losing body weight and, particularly, excess visceral adiposity seems to be necessary to minimize the risk of cardiometabolic diseases.

Cardiovascular risk factors across different levels of urbanization in Brazilian Afro‐derived communities ( quilombos )

Article

Full-text available

Nov 2022

Objectives: The frequency of cardiovascular diseases has increased throughout the world. People of African descent have been disproportionately affected, particularly if they reside in urban settings. In this work, we evaluate risk factors associated with cardiovascular diseases (CVD) and other chronic diseases in rural and urban Afro-derived communities (quilombo) in Central Brazil. We also determine if there are associations between the frequency of CVD risk factors, sex, and proximity to urban environments. Methods: Through a cross-sectional study of participants (n = 347) within three Brazilian Afro-derived communities: Kalunga (a semi-isolated rural community; n = 214), Cocalinho (a non-isolated rural village; n = 70), and Pé do Morro (an urban community; n = 63), we collected data regarding chronic disease (i.e., CVD, diabetes, and hypertension) risk through questionnaires, anthropometrics, blood pressure, and blood samples using standard protocols. Differences between variables were tested by the Chi-square test of Pearson and Fisher's Exact Test, independent sample t-tests, analysis of variances, and Kruskal-Wallis tests (p ≤ .05). Results: The prevalence of hypertension, overweight, obesity, and other cardiovascular risk factors were higher in the non-isolated rural and urban communities than in the semi-isolated rural community. We found significant sex differences in the distribution of the CVD risk factors, with all occurring at a higher frequency among females. Conclusions: Our findings indicate that Brazilian Afro-derived communities are currently going through an epidemiological transition. The urban lifestyle and its environmental factors are likely contributing to an escalation in cardio-metabolic disease risk. However, the magnitude of this transition differentially impacts the sexes, as females suffer a higher frequency of risk factors compared to males.

The evolution of human step counts and its association with the risk of chronic disease

Article

Nov 2022
CURR BIOL

Walking - humans' most fundamental form of moderate intensity physical activity - is associated with reduced risks of morbidity and mortality. Evolutionary perspectives have contributed much to understanding the effects of walking and other physical activities on health; however, we know comparatively little about how step counts (steps taken per day) changed over the course of human evolution, potentially affecting how selection operated on physiological responses to moderate intensity physical activity that influence morbidity and mortality. Here, we compare step counts across humans and our closest living relatives, the great apes. Compiling data from epidemiology and comparative physiology, we show how step counts more than tripled during human evolution, potentially linking higher levels of moderate intensity physical activity with reduced morbidity and mortality, and we highlight how recent decreases in step counts are an evolutionary mismatch. We raise the hypothesis that the dose-response relationship between moderate intensity physical activity and health was shifted in humans to require more steps per day to promote extended healthspan and lifespan.

Primordial Prevention of Atherosclerotic Cardiovascular Disease: A REVIEW OF THE LITERATURE

Article

Nov 2022

Purpose: The primordial prevention of atherosclerotic cardiovascular disease (ASCVD) involves the prevention of the onset of its risk factors. This review explores the associations between early modifiable risk factors and the development of ASCVD in adulthood, as well as evidence-based interventions to prevent them. Review methods: A review was conducted on the basis of an in-depth literature search including longitudinal observational data, systematic reviews and meta-analyses published in 2012 or later, clinical trials, and additional manual searches of recent literature based on reference lists of other reviews and relevant guidelines. Summary: ASCVD is a disease that begins in childhood; hence, primordial prevention is an important target for improving cardiovascular morbidity and mortality later in life. Data from large-scale population studies have consistently identified the following modifiable risk factors for the development of ASCVD: smoking, overweight and obesity, high cholesterol, high blood pressure, hyperglycemia, poor diet, and physical inactivity. These risk factors originate during the prenatal, childhood, and adolescent stages of life. Various successful interventions to prevent the onset of each risk factor have been evaluated at the individual, community, and population levels. Implementation of a heart-healthy dietary pattern and regular exercise early in life are large components of many successful interventions.

Cardiovascular Risk Assessment and Management for Pediatricians

Article

Nov 2022
Pediatrics

Childhood and adolescence provide a unique window of opportunity to prevent atherosclerotic cardiovascular disease later in life, especially for pediatric groups at risk. The growing list of pediatric groups at risk includes individuals with chronic inflammatory disorders, organ transplants, familial hypercholesterolemia, endocrine disorders, childhood cancer, chronic kidney diseases, congenital heart diseases, and premature birth, as well as increasing numbers of children and adolescents with traditional risk factors such as obesity, hypertension, hyperlipidemia, and hyperglycemia. Here, we focus on recent advances in cardiovascular risk assessment and management and their implications for pediatric practice. First, hyperlipidemia and hyperglycemia are highly prevalent in the young, with hyperlipidemia occurring in 14.6% and hyperglycemia in 16.4% of children and adolescents with a normal weight. Implementation of nonfasting lipid and glycated hemoglobin screening in youth at risk is emerging as a promising avenue to improve testing compliance and lipid and glucose management. Second, blood pressure, lipid, and glucose management in youth at risk are reviewed in depth. Third, multisite and multimodal assessment of early atherosclerosis is discussed as a way to capture the complexity of atherosclerosis as a systemic disease. In addition to conventional carotid intima-media thickness measurements, the measurement of aortic pulse wave velocity and peripheral arterial tonometry can advance the assessment of early atherosclerosis in pediatrics. Finally, we make a plea for lifetime atherosclerotic cardiovascular disease risk stratification that integrates disease-associated risk factors and traditional risk factors and could facilitate tailored cardiovascular risk management in growing numbers of children and adolescents at risk.

Generational issues in linking family farming production, traditional food in diet, physical activity and obesity in Pacific Islands countries and territories: the case of the Melanesian population on Lifou Island

Article

Oct 2022

In the Melanesian culture, traditional activities are organized around family farming, although the lifestyle transition taking place over the last several decades has led to imbalances in diet and physical activity, with both leading to obesity. The aim of this interdisciplinary study was to understand the links between family farming (produced, exchanged, sold, and consumed food), diet (focused on produced, hunted, and caught food), physical activity (sedentary, light, and moderate-to-vigorous physical activity) and obesity in Melanesian Lifou Island families (parents and children). Forty families, including 142 adults and children, completed individual food frequency questionnaires, wore tri-axial accelerometers for seven continuous days, and had weight and height measured with a bio-impedance device. A family farming questionnaire was conducted at the household level concerning family farming practices and sociodemographic variables. Multinomial regression analyses and logistic regression models were used to analyze the data. Results showed that family farming production brings a modest contribution to diet and active lifestyles for the family farmers of Lifou Island. The drivers for obesity in these tribal communities were linked to diet in the adults, whereas parental socioeconomic status and moderate-to-vigorous physical activity were the main factors associated to being overweight and obesity in children. These differences in lifestyle behaviors within families suggest a transition in cultural practices at the intergenerational level. Future directions should consider seasonality and a more in-depth analysis of diet including macro- and micro- nutrients to acquire more accurate information on the intergenerational transition in cultural practices and its consequences on health outcomes in the Pacific region.

Schizophrenia: The new etiological synthesis

Article

Full-text available

Sep 2022
NEUROSCI BIOBEHAV R

Schizophrenia has been an evolutionary paradox: it has high heritability, but it is associated with decreased reproductive success. The causal genetic variants underlying schizophrenia are thought to be under weak negative selection. To unravel this paradox, many evolutionary explanations have been suggested for schizophrenia. We critically discuss the constellation of evolutionary hypotheses for schizophrenia, highlighting the lack of empirical support for most existing evolutionary hypotheses—with the exception of the relatively well supported evolutionary mismatch hypothesis. It posits that evolutionarily novel features of contemporary environments, such as chronic stress, low-grade systemic inflammation, and gut dysbiosis, increase susceptibility to schizophrenia. Environmental factors such as microbial infections (e.g., Toxoplasma gondii) can better predict the onset of schizophrenia than polygenic risk scores. However, researchers have not been able to explain why only a small minority of infected people develop schizophrenia. The new etiological synthesis of schizophrenia indicates that an interaction between host genotype, microbe infection, and chronic stress causes schizophrenia, with neuroinflammation and gut dysbiosis mediating this etiological pathway. Instead of just alleviating symptoms with drugs, the parasite x genotype x stress model emphasizes that schizophrenia treatment should focus on detecting and treating possible underlying microbial infection(s), neuroinflammation, gut dysbiosis, and chronic stress.

When the flood passes, does health return? A short panel examining water and food insecurity, nutrition, and disease after an extreme flood in lowland Bolivia

Article

Sep 2022

Objectives: Flooding is the most frequent extreme-weather disaster and disproportionately burdens marginalized populations. This article examines how food and water insecurity, blood pressure (BP), nutritional status, and diarrheal and respiratory illnesses changed during the 2 months following a historic flood in lowland Bolivia. Methods: Drawing on longitudinal data from Tsimane' forager-horticulturalist (n = 118 household heads; n = 129 children) directly after a historic 2014 flood and ~2 months later, we use fixed effects linear regression and random effects logistic regression models to test changes in the markers of well-being and health over the recovery process. Results: Results demonstrated that water insecurity scores decreased significantly 2 month's postflood, while food insecurity scores remained high. Adults' systolic and diastolic BP significantly declined 2 months after the flood's conclusion. Adults experienced losses in measures of adiposity (BMI, sum of four skinfolds, waist circumference). Children gained weight and BMI-for-age Z-scores indicating buffering of children by adults from food stress that mainly occurred in the community closer to the main market town with greater access to food aid. Odds of diarrhea showed a nonsignificant decline, while cough increased significantly for both children and adults 2 months postflood. Conclusions: Water insecurity and BP improved during the recovery process, while high levels of food insecurity persisted, and nutritional stress and respiratory illness worsened. Not all indicators of well-being and health recover at the same rate after historic flooding events. Planning for multiphase recovery is critical to improve health of marginalized populations after flooding.

Feeding Our Microbiota: Stimulation of the Immune/Semiochemical System and the Potential Amelioration of Non-Communicable Diseases

Article

Full-text available

Aug 2022

"Non-communicable diseases are those conditions to which the causative infectious agents cannot be readily assigned. It is increasingly likely that at least some of these conditions are due to the breakdown of the previously mutualistic gut microbiota under the influence of a polluted, biocide-rich environment... a more cogent explanation for all the available facts is that the fully functioning, adequately diverse microbiome, communicating through what has been termed the microbiota–gut–brain axis, helps to control the passage of food through the digestive tract to provide itself with the nutrition it needs. The method of communication is via the production of semiochemicals, interkingdom signalling molecules... In turn, the microbiome aids the immune system of both adult and, most importantly, the neonate. In this article we consider the role of probiotics and prebiotics, including fermented foods and dietary fibre, in the stimulation of the immune system and of semiochemical production in the gut lumen. Finally, we reprise our suggestion of an ingestible sensor, calibrated to the detection of such semiochemicals, to assess both the effectiveness of individual microbiomes and methods of amelioration of the associated non-communicable diseases"

Sedentary behavior and cardiovascular disease risk: An evolutionary perspective

Article

Full-text available

Jul 2022

A ubiquitous aspect of contemporary societies is sedentary behavior (SB), defined as low intensity activities in a seated, reclined, or supine posture. Leading public health agencies, including the World Health Organization, have recognized the strong association between SB and poor health outcomes, particularly cardiovascular disease. However, while public health agencies have begun to advocate for “reductions” in SB, the current US guidelines are typically vague and non-specific. There is good reasoning behind this non-committal advocacy—there is limited mechanistic and clinical evidence to support policy development. To guide SB policy development, it is important to first consider the origins and evolution of SB, including the following: 1) is SB really a novel/contemporary behavior? i.e., how has this behavior evolved? 2) how did our ancestors sit and in what contexts? 3) how does SB interact with 24-hour activity behaviors, including physical activity and sleep? 4) what other historical and contemporary facets of life interact with SB? and 5) in what context do these behaviors occur and how might they provide different evolutionarily novel stressors? This perspective article will synthesize the available evidence that addresses these questions and stimulate discussion pertaining to the lessons that we can learn from an historical and evolutionary perspective. Last, it will outline the gaps in current SB interruption literature that are hindering development of feasible SB reduction policy.

Nye suksesskriterier for sunn mat

Article

Dec 2017

Evaluate the activity of arginase and some biochemical parameters in patients with atherosclerosis

Conference Paper

Jul 2022

The study includes determination of the activity of arginase and some biochemical parameters in sera of patients with atherosclerosis, 90 serum samples were collected 60 specimens from patients with atherosclerosis, and 30 specimen from the control group, collected from Balad general hospital from the period between October to December 2020, with age range between 35-70 year.The study includes determination of serum arginase activity and the concentration of serum lipid profile (cholesterol, Triglycerides-TG, High-density lipoprotein cholesterol-HDL-C, Low- density lipoprotein cholesterol-LDL-C, and very Low-density cholesterol-VLDL) Malondialdehyde-MDA, Glutathione-GSH and total antioxidant capacity-TAC in sera of patients with atherosclerosis and control group. The results indicate that the activity of arginase significantly elevated in sera of patients group as compared with control, and also the level of cholesterol, TG, LDL-C, VLDL significantly elevated in sera of patients group as compared with control, While the level of HDL-C and TAC were significantly decreased, with no significant change in MDA and GSH between the two groups.

Actualités dans la physiopathologie de l'athérosclérose

Article

Jun 2022

Alain Tedgui

Résumé L’athérosclérose est initiée par l’accumulation sous-endothéliale de lipoprotéines de faible densité (LDL), lesquelles après oxydation déclenchent une réaction inflammatoire locale faisant intervenir principalement les mono- cytes/macrophages et les lymphocytes T et B. Les cellules musculaires lisses vasculaires se différencient en myofibroblastes pour sécréter des fibres de collagène, constituants de la chape fibreuse qui assure la stabilisation de la plaque. Au-delà des facteurs de risque cardiovasculaire classiques, un nouveau facteur de risque de l’athérosclérose a récemment été identifié : l’hématopoïèse clonale. De multiples stratégies thérapeutiques avec un réel bénéfice clinique sont aujourd’hui disponibles pour modifier les principaux facteurs de risque, dont le cholestérol et l’hypertension. Mais de nouveaux traitements spécifiquement conçus pour lutter contre l’inflammation commencent à faire la preuve de leur efficacité.

Detecting Coronary Calcium in Young Adults

Article

May 2022
J AM COLL CARDIOL

A health and lifestyle framework: An evidence‐informed basis for contemporary physical therapist clinical practice guidelines with special reference to individuals with heart failure

Article

Full-text available

Apr 2022

Background and purpose: This study proposes contemporary physical therapist clinical practice guidelines (CPGs) with special reference to heart failure (HF) be grounded in an evidence-informed integrative health and lifestyle framework to not only better reflect the totality and weighting of the literature, but also in the interest of superior patient, clinical, and economic outcomes. Methods: As an illustration, a health and lifestyle framework is described to underpin, thereby complement, recently published physical therapist CPGs for individuals with HF. Results: The case for the framework, an alternative to a single-disease biomedical perspective, is consistent with 21st century professional and epidemiologic indicators. Four themes that emerged from the HF CPGs and further support such a framework, emerged that is, limitations of conventionally constructed CPGs; physical therapists' scope of practice as "health" professionals; "best" practice in an era of NCDs including HF; and superior economic benefit. Discussion: A health and lifestyle framework underpinning contemporary physical therapist CPGs will enable clinicians to better appreciate the power of lifestyle change in maximizing the health of the heart, its healing and repair, and in mitigating and reversing signs and symptoms of cardiac dysfunction. Further, a focus on health and lifestyle will augment the benefits of the core, evidence-based, key action statements related to exercise in the HF CPGs.

Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease

Article

Full-text available

Nov 2016

Background Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease. The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown. Methods Using a polygenic score of DNA sequence polymorphisms, we quantified genetic risk for coronary artery disease in three prospective cohorts — 7814 participants in the Atherosclerosis Risk in Communities (ARIC) study, 21,222 in the Women’s Genome Health Study (WGHS), and 22,389 in the Malmö Diet and Cancer Study (MDCS) — and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available. We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors: no current smoking, no obesity, regular physical activity, and a healthy diet. Results The relative risk of incident coronary events was 91% higher among participants at high genetic risk (top quintile of polygenic scores) than among those at low genetic risk (bottom quintile of polygenic scores) (hazard ratio, 1.91; 95% confidence interval [CI], 1.75 to 2.09). A favorable lifestyle (defined as at least three of the four healthy lifestyle factors) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle (defined as no or only one healthy lifestyle factor), regardless of the genetic risk category. Among participants at high genetic risk, a favorable lifestyle was associated with a 46% lower relative risk of coronary events than an unfavorable lifestyle (hazard ratio, 0.54; 95% CI, 0.47 to 0.63). This finding corresponded to a reduction in the standardized 10-year incidence of coronary events from 10.7% for an unfavorable lifestyle to 5.1% for a favorable lifestyle in ARIC, from 4.6% to 2.0% in WGHS, and from 8.2% to 5.3% in MDCS. In the BioImage Study, a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category. Conclusions Across four studies involving 55,685 participants, genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. Among participants at high genetic risk, a favorable lifestyle was associated with a nearly 50% lower relative risk of coronary artery disease than was an unfavorable lifestyle. (Funded by the National Institutes of Health and others.)

Immune Function in Amazonian Horticulturalists

Article

Full-text available

May 2016

Background: Amazonian populations are exposed to diverse parasites and pathogens, including protozoal, bacterial, fungal and helminthic infections. Yet much knowledge of the immune system is based on industrialised populations where these infections are relatively rare. Aim: This study examines distributions and age-related differences in 22 measures of immune function for Bolivian forager-horticulturalists and US and European populations. Subjects and methods: Subjects were 6338 Tsimane aged 0-90 years. Blood samples collected between 2004-2014 were analysed for 5-part blood differentials, C-reactive protein, erythrocyte sedimentation rate (ESR) and total immunoglobulins E, G, A and M. Flow cytometry was used to quantify naïve and non-naïve CD4 and CD8 T cells, natural killer cells, and B cells. Results: Compared to reference populations, Tsimane have elevated levels of most immunological parameters, particularly immunoglobulins, eosinophils, ESR, B cells, and natural killer cells. However, monocytes and basophils are reduced and naïve CD4 cells depleted in older age groups. Conclusion: Tsimane ecology leads to lymphocyte repertoires and immunoglobulin profiles that differ from those observed in industrialised populations. These differences have consequences for disease susceptibility and co-vary with patterns of other life history traits, such as growth and reproduction.

Low- vs. Standard-dose coronary artery calcium scanning

Article

Full-text available

Nov 2014

Aims: This study was designed to assess the accuracy of coronary artery calcium scans (CACS) acquired at radiation doses below mammography and low-dose lung scanning, compared with standard-dose CACS. Methods and results: CACS was performed in 102 consecutive patients at 120 kVp; all were imaged at standard-dose mAs levels ranging from 30 to 80 mAs determined by their weight, with iterative reconstruction (IR) level 3, and at 50% of the standard-dose mAs with IR level 7 to compensate for the expected increased noise with lower mAs. The low- vs. standard-dose mAs was 24.5 ± 8.8 vs. 48.5 ± 17.8 mAs (P < 0.0001), and the radiation exposure was 0.37 ± 0.16 vs. 0.76 + 0.34 mSv (P < 0.0001). The Agatston score correlation between the low and high dose was excellent (r = 0.998, P < 0.0001) over a range of scores from 0 to 2512. The weighted kappa for agreement of standard CAC risk categories was 0.95 (95% CI 0.83-0.97). The mean of the differences between individual low- and standard-dose Agatston scores was 17.4 ± 25.8, lower than the reported variability of two scans performed with the same mAs. Conclusion: There was excellent agreement of CACS-based risk classification at low and standard doses, with lower interscan variability than with reported identical doses. The low-dose CACS radiation exposure was less than the approved screening tools of mammography and low-dose lung scanning.

Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan The Multi-Ethnic Study of Atherosclerosis and the Shiga Epidemiological Study of Subclinical Atherosclerosis

Article

Full-text available

Aug 2014
AM J EPIDEMIOL

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000–2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups.

Rapid Screening for Subclinical Atherosclerosis by Carotid Ultrasound Examination: The HAPPY (Heart Attack Prevention Program for You) Substudy

Article

Full-text available

Jun 2013

Cardiovascular disease (CVD)-related death rates have been escalating in emerging economies such as India. A strategy to initiate prophylactic medical intervention by direct identification of subclinical atherosclerotic burden may be appropriate in rural populations where assessment based on traditional risk factors is not available.Objectives This study sought to investigate the feasibility of performing rapid automated carotid ultrasound studies in a rural setting and to measure the prevalence of carotid plaques and age-specific distribution of carotid intima-media thickness (IMT) as an index of subclinical atherosclerosis.Methods Screening of the extracranial carotid system with automated B-mode ultrasound was performed along with health questionnaire assessments in 771 asymptomatic volunteers (ages 40 ± 14 years; 626 men and 145 women) with no known CVD. Measurements of IMT were recorded as the mean of 24 spatial measurements performed over a 1-cm region in the far wall of the common carotid artery at end diastole; the prevalence of the plaque (focal IMT >1.5 mm) was determined.ResultsA total of 69 (8.9%) subjects had atherosclerotic plaques. Of these, 16 (2.1%) exhibited bilateral plaques, 28 (3.6%) left carotid plaque only, and 25 (3.2%) had right carotid plaques. Patients even under 50 years showed a high prevalence of carotid plaques (7%), which increased with age (25% and 35% for 51 to 70 and >70 years, respectively). Only 3 (4.3%) participants with plaques were former smokers. Global mean IMT was 0.55 ± 0.13 mm and correlated with age for both left and right carotid arteries (r = 0.61 and 0.60, p < 0.001 for both) in male as well as female subjects (r = 0.70 and 0.67, p < 0.001 for both), respectively.Conclusions Rapid community screening for subclinical atherosclerosis is feasible with automated carotid ultrasound examination and may be beneficial in rural communities of industrializing nations where traditional CVD risk factor data are not yet readily available.

Physical Activity and Modernization Among Bolivian Amerindians

Article

Full-text available

Jan 2013
PLOS ONE

Background: Physical inactivity is a growing public health problem, and the fourth leading risk factor for global mortality. Conversely, indigenous populations living traditional lifestyles reportedly engage in vigorous daily activity that is protective against non-communicable diseases. Here we analyze physical activity patterns among the Tsimane, forager-horticulturalists of Amazonian Bolivia with minimal heart disease and diabetes. We assess age patterns of adult activity among men and women, test whether modernization affects activity levels, and examine whether nascent obesity is associated with reduced activity. Methods and findings: A factorial method based on a large sample of behavioral observations was employed to estimate effects of age, sex, body mass index, and modernization variables on physical activity ratio (PAR), the ratio of total energy expenditure to basal metabolic rate. Accelerometry combined with heart rate monitoring was compared to the factorial method and used for nighttime sampling. Tsimane men and women display 24 hr physical activity level (PAL) of 2.02-2.15 and 1.73-1.85, respectively. Little time was spent "sedentary", whereas most activity was light to moderate, rather than vigorous. Activity peaks by the late twenties in men, and declines thereafter, but remains constant among women after the early teens. Neither BMI, fat free mass or body fat percentage are associated with PAR. There was no negative effect of modernization on physical activity. Conclusions: Tsimane display relatively high PALs typical of other subsistence populations, but of moderate intensity, and not outside the range of developed populations. Despite rapidly increasing socioeconomic change, there is little evidence that total activity has yet been affected. Overweight and obesity are more prevalent among women than men, and Spanish fluency is associated with greater obesity in women. The lack of cardiovascular disease among Tsimane is unlikely caused by activity alone; further study of diet, food intake and infectious disease is needed.

Risk of Cardiovascular Disease in a Traditional African Population with a High Infectious Load: A Population-Based Study

Article

Full-text available

Oct 2012
PLOS ONE

To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%). Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

Fatty Acid Composition in the Mature Milk of Bolivian Forager-Horticulturalists: Controlled Comparisons With a US Sample

Article

Full-text available

May 2012
MATERN CHILD NUTR

Breast milk fatty acid (FA) composition varies greatly among individual women, including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6 (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are important for infant neurological development. It has been suggested that owing to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk FA composition should be derived from populations consuming traditional diets. We collected breast milk samples from Tsimane women at varying lactational stages (6-82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level population living in Amazonia Bolivia. Tsimane samples were matched by lactational stage to samples from a US milk bank, and analysed concurrently for FA composition by gas-liquid chromatography. We compared milk FA composition between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in LCPUFA percentages that may be due to population-typical dietary patterns. Per total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic acid) and trans FAs were significantly higher among US mothers. Tsimane mothers' higher milk n-3 and n-6 LCPUFA percentages may be due to their regular consumption of wild game and freshwater fish, as well as comparatively lower intakes of processed foods and oils that may interfere with LCPUFA synthesis.

Atherosclerosis in Ancient Egyptian Mummies The Horus Study

Article

Full-text available

Mar 2011

The purpose of this study was to determine whether ancient Egyptians had atherosclerosis. The worldwide burden of atherosclerotic disease continues to rise and parallels the spread of diet, lifestyles, and environmental risk factors associated with the developed world. It is tempting to conclude that atherosclerotic cardiovascular disease is exclusively a disease of modern society and did not affect our ancient ancestors. We performed whole body, multislice computed tomography scanning on 52 ancient Egyptian mummies from the Middle Kingdom to the Greco-Roman period to identify cardiovascular structures and arterial calcifications. We interpreted images by consensus reading of 7 imaging physicians, and collected demographic data from historical and museum records. We estimated age at the time of death from the computed tomography skeletal evaluation. Forty-four of 52 mummies had identifiable cardiovascular (CV) structures, and 20 of these had either definite atherosclerosis (defined as calcification within the wall of an identifiable artery, n = 12) or probable atherosclerosis (defined as calcifications along the expected course of an artery, n = 8). Calcifications were found in the aorta as well as the coronary, carotid, iliac, femoral, and peripheral leg arteries. The 20 mummies with definite or probable atherosclerosis were older at time of death (mean age 45.1 ± 9.2 years) than the mummies with CV tissue but no atherosclerosis (mean age 34.5 ± 11.8 years, p < 0.002). Two mummies had evidence of severe arterial atherosclerosis with calcifications in virtually every arterial bed. Definite coronary atherosclerosis was present in 2 mummies, including a princess who lived between 1550 and 1580 BCE. This finding represents the earliest documentation of coronary atherosclerosis in a human. Definite or probable atherosclerosis was present in mummies who lived during virtually every era of ancient Egypt represented in this study, a time span of >2,000 years. Atherosclerosis is commonplace in mummified ancient Egyptians.

Long-Term Follow-up after Tight Control of Blood Pressure in Type 2 Diabetes

Article

Full-text available

Oct 2008
NEW ENGL J MED

Post-trial monitoring of patients in the United Kingdom Prospective Diabetes Study (UKPDS) examined whether risk reductions for microvascular and macrovascular disease, achieved with the use of improved blood-pressure control during the trial, would be sustained. Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus, we randomly assigned, over a 4-year period beginning in 1987, 1148 patients with hypertension to tight or less-tight blood-pressure control regimens. The 884 patients who underwent post-trial monitoring were asked to attend annual UKPDS clinics for the first 5 years, but no attempt was made to maintain their previously assigned therapies. Annual questionnaires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5, and questionnaires were used for all patients in years 6 to 10. Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis, according to the previous randomization categories. Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial. Significant relative risk reductions found during the trial for any diabetes-related end point, diabetes-related death, microvascular disease, and stroke in the group receiving tight, as compared with less tight, blood-pressure control were not sustained during the post-trial follow-up. No risk reductions were seen during or after the trial for myocardial infarction or death from any cause, but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant (P=0.02). The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost. Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications, but it appears that good blood-pressure control must be continued if the benefits are to be maintained. (UKPDS 81; Current Controlled Trials number, ISRCTN75451837.)

Amount of Time Spent in Sedentary Behaviors in the United States, 2003-2004

Article

Full-text available

May 2008

Sedentary behaviors are linked to adverse health outcomes, but the total amount of time spent in these behaviors in the United States has not been objectively quantified. The authors evaluated participants from the 2003–2004 National Health and Nutrition Examination Survey aged ≥6 years who wore an activity monitor for up to 7 days. Among 6,329 participants with at least one 10-hour day of monitor wear, the average monitor-wearing time was 13.9 hours/day (standard deviation, 1.9). Overall, participants spent 54.9% of their monitored time, or 7.7 hours/day, in sedentary behaviors. The most sedentary groups in the United States were older adolescents and adults aged ≥60 years, and they spent about 60% of their waking time in sedentary pursuits. Females were more sedentary than males before age 30 years, but this pattern was reversed after age 60 years. Mexican-American adults were significantly less sedentary than other US adults, and White and Black females were similarly sedentary after age 12 years. These data provide the first objective measure of the amount of time spent in sedentary behavior in the US population and indicate that Americans spend the majority of their time in behaviors that expend very little energy.

Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups

Article

Full-text available

Mar 2008
NEW ENGL J MED

In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

Miami Multiple Risk Factor Intervention Trial(MRFIT)

Chapter

Jan 1981

In 1971 a Task Force on Atherosclerosis appointed by the National Heart and Lung Institute recommended the development and support of a preventive trial in men with multiple coronary heart disease risk factors.1 Previous studies in the United States and abroad have shown that elevated serum cholesterol, hypertension and cigarette smoking are clearly associated with a high incidence of coronary disease.2 The Multiple Risk Factor Intervention Trial (MRFIT) was therefore initiated to test the hypothesis that significant reduction of these three key variables through an intervention program would be associated with decreased morbidity and mortahty from coronary heart disease. From 1972 to 1974, 20 clinical centers were selected to participate.3 The Dade County Department of Pubhc Health in Miami was one of these centers and the only county health department to be included in the national program. In 1976 the Miami MRFIT also became associated with the Nutrition Division of the Department of Epidemiology and Public Health at the University of Miami School of Medicine.

Predictors of Long-Term Healthy Arterial Aging

Article

Nov 2015

This study sought to determine the predictors of healthy arterial aging.

Atherosclerosis Across 4000 Years of Human History: The Horus Study of Four Ancient Populations

Article

Aug 2013
J VASC SURG

Human beings residing in very hot, cold, or dry environments have independently discovered how to mummify dead members of their society. These, often preindustrial, cultures have created the opportunity to study ancient human beings with modern computed tomography scanning to assess the extent of vascular calcifications in diffuse environments and cultures. Calcium is a nearly universal component of a mature atherosclerotic plaque and is pathognomonic for atherosclerosis (Stary HC et al, Circulation 1995;92:1355-74). The authors recently confirmed atherosclerotic calcifications in 20 of 44 Egyptian mummies of individuals who lived during several dynasties between 1981 bc and 364 ce (Common Era) (Allam AH et al, J Am Coll Cardiol Imagining 2011;4:315-27). In this current study the authors examined 137 mummies from populations of four disparate geographic regions. Mummies were studied by whole-body computed tomography scanning and included specimens from Ancient Egypt, the Roman Era, Ancient Peru, and five cultures from Southwest America (ca 1500 bce to 1500 ce, five evacuation sites). Finally, there were five ancient Unargan specimens from the Aleutian Islands of modern-day Alaska. Mummies were selected for imaging on the basis of a good state of preservation and the likelihood of being adult. Random selection was not used. The population examined spanned >4000 years. Atherosclerosis was regarded as definitive if calcified plaque was seen on the wall of an artery and considered probable if artery calcifications were seen along the expected course of an artery. Of the 137 mummies, 47 (34%) demonstrated probable or definitive atherosclerosis: 29 of 76 Ancient Egyptians (38%), 13 of 51 Ancient Peruvians (25%), two of five ancestral Puebloans (40%), and three of five Unangan hunter-gatherers (60%; P = not significant). Atherosclerosis was present in the aorta in 20% of mummies, the iliac/femoral arteries in 18%, the popliteal/tibial arteries in 18%, carotid arteries in 12%. and the coronary arteries in only 4%. Of the five vascular beds examined, atherosclerosis was present in one to two beds in 25% of mummies, in three to four beds in 8%, and all five vascular beds in only 1%. Age and time of death were positively correlated with atherosclerosis: the mean age at death was 43 years (standard deviation [SD], 10 years) for mummies with atherosclerosis vs 32 years (SD, 15 years) for those without (P < .0001). Age also varied with the number of arterial beds involved: the mean age was 32 years (SD, 15 years) for mummies with no atherosclerosis, 42 years (SD, 10 years) for those with atherosclerosis in one or two beds, and 44 years (8 years) for those with atherosclerosis in three to five beds (P < .0001).

Detection of Subclinical Atherosclerosis in Peripheral Arterial Beds With B-Mode Ultrasound

Article

Dec 2014

Objectives: To assess subclinical atherosclerotic cardiovascular disease (ASCVD) using B-mode ultrasound, with special emphasis on the incremental value of performing imaging in multiple peripheral arteries, and to compare imaging findings with traditional risk factors for medical intervention eligibility. Methods: Data from 2 asymptomatic cohorts from India with unknown ASCVD risk factors were compared to 2 cohorts from North America with known ASCVD risk factors. Carotid and iliofemoral arteries of the Indian cohorts were examined with automated ultrasound in a high-pace environment by non-experts. A simplified metric of atherosclerotic disease burden (FUster-Narula or FUN Score) was developed from 3D imaging data by summing intima-media volume (IMV) over 5-cm arterial segments. Effectiveness of ASCVD prevention guidelines to direct therapy was compared to results from direct imaging. Results: Of the 941 (mean age 44.27 ± 13.76 years, 34% female) enrollees from India, 224 (24%) demonstrated plaques in at least 1 of the 4 arterial sites examined; 107 (11%) had plaques in only the carotids, 70 (7%) in both the carotids and iliofemoral arteries, and 47 (5%) had plaques in only the iliofemoral arteries. Older age and male sex were associated with the presence of plaque, but association with systolic blood pressure was not observed. Data from 2 North American clinics (n = 481, mean age 59.68 ± 11.95 years, 39% female) showed that 203 subjects (42%) had carotid plaque; 82% of whom would not have qualified for lipid-lowering therapy under the Adult Treatment Panel (ATP) III Guidelines. Using the recently published ATP IV Guidelines, 33% of the individuals with carotid plaque would also have failed to qualify for treatment. Conclusions: B-mode ultrasound examination of bilateral iliofemoral arteries provided an incremental yield in identifying subclinical atherosclerotic disease compared to carotid evaluation alone. Ultrasound examination allowed improved identification of individuals who could be targeted for prophylactic medical intervention compared to ATP III and ATP IV Guidelines.

Markers of inflammation and cardiovascular disease. AHA/CDC scientific statement

Article

May 2003
J Cardpulm Rehabil

Association of Coronary Artery Calcium and Coronary Heart Disease Events in Young and Elderly Participants in the Multi-Ethnic Study of Atherosclerosis : A Secondary Analysis of a Prospective, Population-Based Cohort

Article

Oct 2014

Objective To evaluate the association of coronary artery calcium (CAC) and coronary heart disease (CHD) events among young and elderly individuals. Participants and Methods This is a secondary analysis of data from a prospective, multiethnic, population-based cohort study designed to study subclinical atherosclerosis. A total of 6809 persons 45 through 84 years old without known cardiovascular disease at baseline were enrolled from July 2000 through September 2002. All participants had CAC scoring performed and were followed up for a median of 8.5 years. The main outcome measures studied were CHD events, defined as myocardial infarction, definite angina or probable angina followed by revascularization, resuscitated cardiac arrest, or death attributable to CHD. Results Comparing individuals with a CAC score of 0 with those with a CAC score greater than 100, there was an increased incidence of CHD events from 1 to 21 per 1000 person-years and 2 to 23 per 1000 person-years in the 45- through 54-year-old and 75- through 84-year-old groups, respectively. Compared with a CAC score of 0, CAC scores of 1 through 100 and greater than 100 impart an increased multivariable-adjusted CHD event risk in the 45- through 54-year-old and 75- through 84-year-old groups (hazard ratio [HR], 2.3; 95% CI, 0.9-5.8; for those 45-54 years old with CAC scores of 1-100; HR, 12.4; 95% CI, 5.1-30.0; for those 45-54 years old with CAC scores >100: HR, 5.4; 95% CI, 1.2-23.8; for those 75-84 years old with CAC scores of 1-100; and HR, 12.1; 95% CI, 2.9-50.2; for those 75-84 years old with CAC scores >100). Conclusion Increased CAC imparts an increased CHD risk in younger and elderly individuals. CAC is highly predictive of CHD event risk across all age groups, suggesting that once CAC is known chronologic age has less importance. The utility of CAC scoring as a risk-stratification tool extends to both younger and elderly patients.

Ethnic Differences in Coronary Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)

Article

Jul 2005

Quantification of Coronary Artery Calcium Using Ultrafast Computed Tomography

Article

Nov 1989
J AM COLL CARDIOL

Progression of Coronary Calcium and Incident Coronary Heart Disease Events MESA (Multi-Ethnic Study of Atherosclerosis)

Article

Mar 2013

Objectives: The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. Background: CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. Methods: We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. Results: A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. Conclusions: Progression of CAC is associated with an increased risk for future hard and total CHD events.

Coronary artery calcium distributions in older persons in the AGES-Reykjavik study

Article

Sep 2012
EUR J EPIDEMIOL

Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an independent risk factor for cardiac events. Here, we describe CAC-distributions in an unselected aged population and compare modelling methods to characterize CAC-distribution. CAC is difficult to model because it has a skewed and zero inflated distribution with over-dispersion. Data are from the AGES-Reykjavik sample, a large population based study [2002-2006] in Iceland of 5,764 persons aged 66-96 years. Linear regressions using logarithmic- and Box-Cox transformations on CAC+1, quantile regression and a Zero-Inflated Negative Binomial model (ZINB) were applied. Methods were compared visually and with the PRESS-statistic, R(2) and number of detected associations with concurrently measured variables. There were pronounced differences in CAC according to sex, age, history of coronary events and presence of plaque in the carotid artery. Associations with conventional coronary artery disease (CAD) risk factors varied between the sexes. The ZINB model provided the best results with respect to the PRESS-statistic, R(2), and predicted proportion of zero scores. The ZINB model detected similar numbers of associations as the linear regression on ln(CAC+1) and usually with the same risk factors.

Does Blood Pressure Inevitably Rise With Age? Longitudinal Evidence Among Forager-Horticulturalists

Article

Jul 2012
Hypertension

The rise in blood pressure with age is a major risk factor for cardiovascular and renal disease, stroke, and type 2 diabetes mellitus. Age-related increases in blood pressure have been observed in almost every population, except among hunter-gatherers, farmers, and pastoralists. Here we tested for age-related increases in blood pressure among Tsimane forager-farmers. We also test whether lifestyle changes associated with modernization lead to higher blood pressure and a greater rate of age-related increase in blood pressure. We measured blood pressure longitudinally on 2248 adults age ≥ 20 years (n=6468 observations over 8 years). Prevalence of hypertension was 3.9% for women and 5.2% for men, although diagnosis of persistent hypertension based on multiple observations reduced prevalence to 2.9% for both sexes. Mixed-effects models revealed systolic, diastolic, and pulse blood pressure increases of 2.86 (P<0.001), 0.95 (P<0.001), and 1.95 mmHg (P<0.001) per decade for women and 0.91 (P<0.001), 0.93 (P<0.001), and -0.02 mmHg (P=0.93) for men, substantially lower than rates found elsewhere. Lifestyle factors, such as smoking and Spanish fluency, had minimal effect on mean blood pressure and no effect on age-related increases in blood pressure. Greater town proximity was associated with a lower age-related increase in pulse pressure. Effects of modernization were, therefore, deemed minimal among Tsimane, in light of their lean physique, active lifestyle, and protective diet.

The prevalence and distribution of coronary artery calcium in asymptomatic Korean population

Article

Jul 2011

Coronary artery calcium score (CACS) is a strong predictor of coronary heart disease and provides incremental prognostic information beyond traditional risk factors. The difference in prevalence and distribution of CACS in different ethnic groups has been reported with conflicting results. We aimed to investigate the prevalence and distribution of CACS in asymptomatic Korean population. A total of 5,239 asymptomatic patients free of known coronary artery disease who had coronary artery calcium scoring computed tomography during comprehensive medical examinations were included in the analysis. Coronary calcium was present in 33.1% of overall population, 40.5% of males and 19.3% of females. In all age groups, CACS was higher in males. The pattern of increase in CACS appeared in different patterns, with earlier and gradual increase in males. In females, there was a time-lag, behind that observed in males by about 10 years. Multivariate analysis showed that male gender (OR 3.759, 95% CI 3.120-4.529, P < 0.001), older age (OR 1.095, 95% CI 1.085-1.106, P < 0.001), pulse pressure (OR 1.142, 95% CI 1.063-1.227, P < 0.001), HbA1C (OR 1.390, 95% CI 1.255-1.540, P < 0.001), and obesity defined by body mass index (BMI) ≥ 25 kg/m(2) (OR 1.042, 95% CI 1.011-1.073, P = 0.007) were related to the presence of coronary artery calcification (CACS > 0). This study provides a healthy reference value of coronary artery calcification in Korean subjects, based on sex and age percentiles. Similar age and gender associations and distributions of coronary artery calcification are found, compared to the previous studies in western populations, but median CACS tend to be lower in Koreans.

The Role of C-Reactive Protein as a Risk Predictor of Coronary Atherosclerosis: Implications from the JUPITER Trial

Article

Apr 2011
Curr Atherosclerosis Rep

Much controversy surrounds the use of high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular (CV) risk. Although data regarding the association of hs-CRP with CV disease is extensive and consistent, its role in clinical practice remains unclear. The American Heart Association (AHA) recently published a scientific statement regarding criteria for evaluation of novel markers of CV risk. This article provides a comprehensive review of data regarding hs-CRP as a risk marker for CV disease in the context of these AHA criteria. The impact of the JUPITER trial on the utility of hs-CRP as a risk marker is emphasized. The review concludes with an evidence-based statement regarding the current role of hs-CRP in CV risk prediction.

Blood Lipids, Infection, and Inflammatory Markers in the Tsimane of Bolivia

Article

Nov 2010
AM J HUM BIOL

Little is known about blood cholesterol (blood-C) levels under conditions of infection and limited diet. This study examines blood-C and markers of infection and inflammation in the Tsimane of the Bolivian Amazon, indigenous forager farmers living in conditions that model preindustrial European populations by their short life expectancy, high load of infections and inflammation, and limited diets. We use multivariate models to determine the relationships between lipid levels and markers of infection and inflammation. Adult Tsimane (N = 418, age 20-84) were characterized for blood lipids, cells, and inflammatory markers in relation to individual loads of parasites and village region. Most of the Tsimane (60%) carried at least one parasite species, averaging 1.3 species per person. Serum high-density lipoprotein cholesterol (HDL-C), total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) were below the U.S. norms and varied inversely with markers of infection and inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), immunoglobulin (Ig) E and eosinophil count. Although no relationship of parasite load to blood-C was found, there was an association between anemia and parasite prevalence. We conclude that the highly infected environment of the Tsimane is related to low levels of blood total-C, HDL-C, and LDL-C. This may suggest a potential reason why arterial disease is largely absent in the Tsimane.

PCSK9 R46L, Low-Density Lipoprotein Cholesterol Levels, and Risk of Ischemic Heart Disease 3 Independent Studies and Meta-Analyses

Article

Jun 2010

The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality. The 46L allele has been associated with reductions in LDL-C and risk of IHD, but results vary between studies. We determined the association of R46L genotype with LDL-C, risk of IHD, myocardial infarction (MI), and mortality in the prospective CCHS (Copenhagen City Heart Study) (n = 10,032) and validated the results in: 1) the cross-sectional CGPS (Copenhagen General Population Study) (n = 26,013); and 2) the case-control CIHDS (Copenhagen Ischemic Heart Disease Study) (n = 9,654). We also performed meta-analyses of present and previous studies (n = 66,698). In carriers (2.6%) versus noncarriers, the 46L allele was associated with reductions in LDL-C of 0.35 to 0.55 mmol/l (11% to 16%) from 20 to 80+ years in the general population (CCHS and CGPS; p values <0.0001). Observed risk reductions for IHD in 46L allele carriers were: 6% in the CCHS study (hazard ratio [HR]: 0.94; 95% confidence interval [CI]: 0.68 to 1.31), 46% in the CGPS study (odds ratio [OR]: 0.54; 95% CI: 0.39 to 0.77), 18% in the CIHDS study (OR: 0.82; 95% CI: 0.55 to 1.21), and 30% in the studies combined (OR: 0.70; 95% CI: 0.58 to 0.86). In the CCHS study, HR for mortality was 1.18 (95% CI: 0.93 to 1.50). In meta-analyses, 46L allele carriers had a 12% (0.43 mmol/l) reduction in LDL-C and a 28% reduction in risk of IHD (HR: 0.72; 95% CI: 0.62 to 0.84), similar to results in the CCHS, CGPS, and CIHDS studies combined. However, the observed 12% (0.43 mmol/l) reduction in LDL-C theoretically predicted an only 5% reduction in risk of IHD (HR: 0.95; 95% CI: 0.92 to 0.97). The PCSK9 46L allele was associated with reductions in LDL-C from 20 to 80+ years in the general population. The reduction in risk of IHD was larger than predicted by the observed reduction in LDL-C alone. This could be because genotype is a better predictor of lifelong exposure to LDL-C than LDL-C measured in adult life.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients

Article

Apr 2010
EUR J CLIN INVEST

The magnitude of lipoprotein level reduction during the acute-phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis. This is a prospective cohort study and case-control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group. Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0.969; 95% CI: 0.944-0.995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (Delta CETP) was more pronounced in non-survivors (0.78 +/- 1.08 microg mL(-1)) than that in survivors (0.02 +/- 0.58 microg mL(-1), P = 0.01). HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL(-1) increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.

Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte Jr M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15, 827-832

Article

Apr 1990
J AM COLL CARDIOL

Ultrafast computed tomography was used to detect and quantify coronary artery calcium levels in 584 subjects (mean age 48 +/- 10 years) with (n = 109) and without (n = 475) clinical coronary artery disease. Fifty patients who underwent fluoroscopy and ultrafast computed tomography were also evaluated. Twenty contiguous 3 mm slices were obtained of the proximal coronary arteries. Total calcium scores were calculated based on the number, areas and peak Hounsfield computed tomographic numbers of the calcific lesions detected. In 88 subjects scored by two readers independently, interobserver agreement was excellent with identical total scores obtained in 70. Ultrafast computed tomography was more sensitive than fluoroscopy, detecting coronary calcium in 90% versus 52% of patients. There were significant differences (p less than 0.0001) in mean total calcium scores for those with versus those without clinical coronary artery disease by decade: 5 versus 132, age 30 to 39 years; 27 versus 291, age 40 to 49 years; 83 versus 462, age 50 to 59 years; and 187 versus 786, age 60 to 69 years. Sensitivity, specificity and predictive values for clinical coronary artery disease were calculated for several total calcium scores in each decade. For age groups 40 to 49 and 50 to 59 years, a total score of 50 resulted in a sensitivity of 71% and 74% and a specificity of 91% and 70%, respectively. For age group 60 to 69 years, a total score of 300 gave a sensitivity of 74% and a specificity of 81%. The negative predictive value of a 0 score was 98%, 94% and 100% for age groups 40 to 49, 50 to 59 and 60 to 69 years, respectively. Ultrafast computed tomography is an excellent tool for detecting and quantifying coronary artery calcium.

A clinical and electrocardiographic study of !Kung Bushmen

Article

Sep 1972

Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk Factors, Evaluation of Coronary Calcium and Lifestyle

Article

Sep 2002

In view of consistently high cardiovascular morbidity and mortality rates, international efforts are aimed at developing tools for more precise risk prediction to allow preventive treatment targeted at high-risk individuals. Direct visualization of anatomic, preclinical atherosclerotic disease has the potential for individualized risk discrimination. Further, a variety of risk factors are actively evaluated, including markers of the activity of atherosclerotic disease, thrombogenic risk, and genetic polymorphisms. The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) study is a population-based, prospective cohort study of the comparative value of modern risk stratification techniques for "hard" c

Coronary Atherosclerosis in Indigenous South American Tsimane: A Cross-Sectional Cohort Study

Abstract

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